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Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
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Journal Article
Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
2023
Overview
Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent—the naked mole-rat
1
,
2
. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmr
Has2
). nmr
Has2
mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmr
Has2
mice shifted towards that of longer-lived species. The most notable change observed in nmr
Has2
mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmr
Has2
gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.
Mice overexpressing
Has2
from the naked mole-rat showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, attenuated inflammation through several pathways, extended lifespan and improved healthspan.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/106
/ 13/109
/ 13/31
/ 45
/ 45/22
/ 45/91
/ Age
/ Aging
/ Animals
/ Cancer
/ Frailty
/ Humanities and Social Sciences
/ Hyaluronan Synthases - genetics
/ Hyaluronan Synthases - metabolism
/ Hyaluronic Acid - biosynthesis
/ Hyaluronic Acid - metabolism
/ Inflammation - prevention & control
/ Mice
/ Neoplasms - prevention & control
/ Science
